Human blood stem cells grown from patient’s own blood cells, for the first time

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HMS researchers have made a mix of blood progenitor cells, shown here, and blood stem cells. Both can generate multiple kinds of blood cells, including red blood cells and lymphocytes. Image: Daley lab

For the first time, scientists have generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.

Since the isolation of human embryonic stem (ES) cells in 1998, scientists have been trying to make blood-forming stem cells, but with little success. In 2007, with the successful generation of induced pluripotent stem cells (iPS) from human skin cells using genetic engineering, scientists have created cell types such as neurons and heart cells, but blood-forming cells has remained elusive.

The latest research from Daley lab opens new avenues for research into the root causes of blood diseases and for creating immune-matched blood cells for treatment purposes that are derived from patients’ own cells.

“We’re tantalizingly close to generating bona fide human blood stem cells in a dish,” said senior investigator George Q. Daley, dean of HMS and head of a research lab in the Stem Cell Program at Boston Children’s. “This work is the culmination of over 20 years of striving.”

Although the cells made from the pluripotent stem cells are a mix of true blood stem cells and other cells known as blood progenitor cells, they proved capable of generating multiple types of human blood cells when put into mice.

“This step opens up an opportunity to take cells from patients with genetic blood disorders, use gene editing to correct their genetic defect and make functional blood cells,” said Ryohichi (Rio) Sugimura, the study’s first author and a postdoctoral fellow in the Daley lab.

“This also gives us the potential to have a limitless supply of blood stem cells and blood by taking cells from universal donors,” said Sugimura. “This could potentially augment the blood supply for patients who need transfusions.”

While human induced pluripotent stem cells (above), created from ordinary skin cells, can make virtually any kind of cell or tissue, blood-forming stem cells have eluded scientists—until now. Image: Daley lab

Sugimura, Daley and colleagues combined two previous approaches to do this.

Firstly, they exposed the patient’s human pluripotent stem cells (both ES and iPS cells) to chemical signals that led to the generation of hemogenic endothelium, an early precursor that eventually gives rise to blood stem cells.

Secondly, the team zeroed in on five likely transcription factors (RUNX1, ERG, LCOR, HOXA5 and HOXA9) from a pool of 26 possible factors that were both necessary and sufficient to create blood stem cells. By using a lentivirus vector, they delivered these factors into the cells. When they transplanted the genetically engineered hemogenic endothelial cells into mice, they observed multiple types of human blood cells in the bone marrow and circulating blood of some of these animals. Some mice were able to mount a human immune response after vaccination.

ES cells and iPS cells were similarly good at creating blood stem and progenitor cells when the technique was applied. But the researchers are most interested in iPS cells, which offer the added ability to derive cells directly from patients and model disease.

“We’re now able to model human blood function in so-called ‘humanized mice,’” said Daley. “This is a major step forward for our ability to investigate genetic blood disease.”

The study, led by Harvard Medical School researchers at Boston Children’s Hospital, was published May 17 in Nature.